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AP Biology
Why do you feel so crappy when a virus invades you?
AP Biology 2007-2008
Immune / LymphaticSystem
lymphocytesattackingcancer cell
phagocytic leukocyte
lymphsystem
Fighting theEnemy Within!
AP Biology
Start and review with the masteringbiology.com Immunology video
Another good one from McGraw-Hill Immune system game by NobelPrize.org
AP Biology
Avenues of attack Points of entry
digestive system respiratory system urogenital tract break in skin
Routes of attack circulatory system lymph system
AP Biology
Why an immune system? Attack from outside
lots of organisms want you for lunch! animals are a tasty nutrient- & vitamin-packed meal
cells are packages of macromolecules animals must defend themselves against invaders (pathogens)
viruses HIV, flu, cold, measles, chicken pox
bacteria pneumonia, meningitis, tuberculosis
Lyme disease fungi
yeast (“Athlete’s foot”…) protists
amoeba, malaria
Attack from inside cancers = abnormal body cells
Mmmmm,What’s in your
lunchbox?
AP Biology
Lines of defense 1st line: Non-specific barriers
broad, external defense “walls & moats”
skin & mucous membranes 2nd line: Non-specific patrols
broad, internal defense “patrolling soldiers”
leukocytes = phagocytic WBC 3rd line: True immune system
specific, acquired immunity “elite trained units”
lymphocytes & antibodies B cells & T cells
Bacteria & insectsinherit resistance.
Vertebratesacquire immunity.
AP Biology
Pathogens(such as bacteria,fungi, and viruses)
INNATE IMMUNITY(all animals)
• Rapid response
Recognition of traits sharedby broad ranges ofpathogens, using a smallset of receptors
•
Recognition of traits specific to particularpathogens, using a vastarray of receptors
•
• Slower response
Barrier defenses:SkinMucous membranesSecretions
Internal defenses:Phagocytic cellsNatural killer cellsAntimicrobial proteinsInflammatory response
Humoral response:Antibodies defend againstinfection in body fluids.
Cell-mediated response:Cytotoxic cells defendagainst infection in body cells.
ADAPTIVE IMMUNITY(vertebrates only)
Figure 43.2
AP Biology
Development of the key players, Red & White blood cells
short-lived phagocytes60-70% WBC
develop into macrophages
inflammatory response
fightparasites
Red blood cells
Lymphocytes
Leukocytes
AP Biology
Thymus
Peyer’spatches(smallintestine)
Appendix(cecum)
AdenoidTonsils
Lymphaticvessels
Spleen
Lymphnodes
Lymphnode
Bloodcapillary
Interstitialfluid
Tissuecells
Lymphatic vessel
Lymphatic vessel
Masses ofdefensive cells
Figure 43.7
AP Biology
1st line: Non-specific External defense Barrier
skin
Traps mucous membranes, cilia,
hair, earwax
Elimination coughing, sneezing, urination,
diarrhea
Unfavorable pH stomach acid, sweat, saliva, urine
Lysozyme enzyme digests bacterial cell walls tears, sweat
Lining of trachea: ciliated cells & mucus secreting cells
AP Biology
2nd line: Non-specific patrolling cells Patrolling cells & proteins
attack pathogens, but don’t “remember” for next time leukocytes
phagocytic white blood cells macrophages, neutrophils,
natural killer cells
complement system Free-floating proteins that
destroy cells
inflammatory response increase in body temp. increase capillary permeability attract macrophages yeast
macrophage
bacteria
AP Biology
Leukocytes: Phagocytic WBCs Attracted by chemical signals released by
damaged cells Neutrophils
most abundant WBC (~70%) ~ 3 day lifespan phagocyte
Macrophages “big eater” phagocyte long-lived
Natural Killer Cells destroy virus-infected cells
& cancer cells
AP Biology
Natural Killer Cells perforate cells release perforin protein insert into membrane of target cell forms pore allowing fluid to
flow in & out of cell cell ruptures (lysis)
apoptosis
Destroying cells gone bad!
perforin puncturescell membrane
cell membrane
natural killer cell
cell membrane
virus-infected cell
vesicle
perforin
AP Biology
Anti-microbial proteins Complement system
~20 proteins circulating in blood plasma attack bacterial & fungal cells
form a membrane attack complex perforate target cell apoptosis
cell lysis
plasma membrane of invading microbe
complement proteinsform cellular lesion
extracellular fluid
complement proteins
bacterial cell
AP Biology
Inflammatory response Damage to tissue triggers
local non-specific inflammatory response release chemical signals
histamines & prostaglandins capillaries dilate, become
more permeable (leaky) delivers macrophages, RBCs,
platelets, clotting factors fight pathogens clot formation
increases temperature decrease bacterial growth stimulates phagocytosis speeds up repair of tissues
AP Biology
Figure 43.8-1
Pathogen Splinter
Mastcell
Macro-phage
Capillary
Redblood cells
Neutrophil
Signalingmolecules
AP Biology
Figure 43.8-2
Pathogen Splinter
Mastcell
Macro-phage
Capillary
Redblood cells
Neutrophil
Signalingmolecules
Movementof fluid
AP Biology
Figure 43.8-3
Pathogen Splinter
Mastcell
Macro-phage
Capillary
Redblood cells
Neutrophil
Signalingmolecules
Movementof fluid
Phagocytosis
AP Biology
Fever When a local response is not enough
system-wide response to infection activated macrophages release interleukin-1
triggers hypothalamus in brain to readjust body thermostat to raise body temperature
higher temperature helps defense inhibits bacterial growth stimulates phagocytosis speeds up repair of tissues causes liver & spleen to store
iron, reducing blood iron levels bacteria need large amounts
of iron to grow
AP Biology
Specific defense with memory lymphocytes
B cells antibodies (a.k.a. immunoglobulins)
T cells
Responds to… antigens
cellular name tags specific pathogens specific toxins abnormal body cells (cancer)
3rd line: Acquired (active) ImmunityB cell
AP Biology“self” “foreign”
How are invaders recognized? Antigens
cellular name tag proteins “self” antigens
no response from WBCs
“foreign” antigens response from WBCs pathogens: viruses, bacteria, protozoa, parasitic worms,
fungi, toxins non-pathogens: cancer cells, transplanted tissue, pollen
AP Biology
Lymphocytes B cells
mature in bone marrow humoral response system
“humors” = body fluids attack pathogens still circulating
in blood & lymph produce antibodies
T cells mature in thymus cellular response system
attack invaded cells
“Maturation” learn to distinguish “self”
from “non-self” antigens if react to “self” antigens, cells
are destroyed during maturation
bone marrow
AP Biology
Humoral (antibody-mediated) immune response Cell-mediated immune response
Antigen (1st exposure)
Engulfed by
Antigen-presenting cell
Helper T cell
Memoryhelper T cells
Antigen (2nd exposure)
B cell
Plasma cells
Secretedantibodies
Defend against extracellularpathogens
Memory B cellsMemory
cytotoxic T cellsActive
cytotoxic T cells
Defend against intracellularpathogens and cancer
Cytotoxic T cell
Key
Stimulates
Gives rise to
Figure 43.20
AP Biology
B cells Attack, learn & remember pathogens
circulating in blood & lymph
Produce specific antibodies against specific antigen
Types of B cells plasma cells
immediate production of antibodies rapid response, short term release
memory cells continued circulation in body long term immunity
AP Biology
macrophage
plasma cellsrelease antibodies
Y
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B cell immune responsetested by
B cells(in blood & lymph)
10 to 17 days for full response
invader(foreign antigen) B cells + antibodies
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recognition
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clones1000s of clone cellsY
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Ymemory cells
“reserves”
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Ycapturedinvaders
AP Biology
Antibodies
Proteins that bind to a specific antigen multi-chain proteins binding region matches molecular shape of antigens each antibody is unique & specific
millions of antibodies respond to millions of foreign antigens
tagging “handcuffs” “this is foreign…gotcha!”
each B cell has ~50,000 antibodies
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antigenantigen-binding site on antibody
variable binding region
AP Biology
ss
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Structure of antibodies
light chains
antigen-bindingsite
heavy chains
antigen-bindingsite
lightchain
B cellmembrane
heavychains
lightchain
variable region
antigen-binding siteY
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AP Biology
What do antibodies do to invaders?
macrophageeating tagged invaders
invading pathogens tagged with antibodiesY
Y
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neutralize capture precipitate apoptosis
AP Biology
Immunoglobulins IgM
1st immune response activate complement proteins
IgG 2nd response, major antibody circulating in plasma promote phagocytosis by macrophages
IgA in external secretions, sweat & mother’s milk
IgE promote release of histamine & lots of bodily fluids evolved as reaction to parasites triggers allergic reaction
IgD receptors of B cells???
macrophageeating tagged
invaders
invading pathogens tagged with antibodies
YY
YY
YYClasses of antibodies
Weeks0 2 4 6
IgM IgG
Exposureto
antigen
An
tib
od
y le
vel
s
AP Biology
Stem cell
Cell division andgene rearrangement
Elimination ofself-reactiveB cells
Clonalselection
Antigen
AntibodyFormation ofactivated cellpopulations
Memory B cells Plasma cells
Pathogen
Receptors bind to antigens
Figure 43.UN02
AP Biology
Vaccinations Immune system exposed
to harmless version of pathogen stimulates B cell system to produce
antibodies to pathogen “active immunity”
rapid response on future exposure creates immunity
without getting disease!
Most successful against viruses
AP Biology
Jonas Salk Developed first vaccine
against polio attacks motor neurons
1914 – 1995April 12, 1955
Albert Sabin1962
oral vaccine
AP Biology
Obtaining antibodies from another individual maternal immunity
antibodies pass from mother to baby across placenta or in mother’s milk
critical role of breastfeeding in infant health mother is creating antibodies against pathogens baby
is being exposed to
Injection injection of antibodies short-term immunity
Passive immunity
AP Biology 2007-2008
What if the attacker gets past the B cells in the blood & actually infects (hides in) some of your cells?
You need trained assassins to recognize & kill off these infected cells!
T
Attackof the
Killer T cells!
But how do T cellsknow someone ishiding in there?
AP Biology
How is any cell tagged with antigens? Major histocompatibility (MHC) proteins
proteins which constantly carry bits of cellular material from the cytosol to the cell surface
“snapshot” of what is going on inside cell give the surface of cells a unique label or
“fingerprint”
T or Bcell
MHC protein
MHC proteinsdisplaying self-antigens
Who goes there?self or foreign?
AP Biology
T cellantigenreceptor
T cell Cytoplasm of T cell
Plasmamembrane
chain chain
Disulfidebridge
Antigen-bindingsite
Variableregions
Constantregions
Transmembraneregion
V V
C C
Figure 43.11
AP Biology
How do T cells know a cell is infected? Infected cells digest some pathogens
MHC proteins carry pieces to cell surface foreign antigens now on cell membrane called Antigen Presenting Cell (APC)
macrophages can also serve as APC tested by Helper T cells
MHC proteins displaying foreign antigens
infectedcell
T cell with antigen receptors
TH cellWANTED
AP Biology
T cells Attack, learn & remember pathogens hiding
in infected cells recognize antigen fragments also defend against “non-self” body cells
cancer & transplant cells
Types of T cells helper T cells
alerts rest of immune system killer (cytotoxic) T cells
attack infected body cells memory T cells
long term immunity
T cell attacking cancer cell
AP Biology
Figure 43.12
Displayedantigenfragment
MHC molecule
Antigenfragment
Pathogen
Host cell
T cell
T cell antigenreceptor
(a) Antigen recognition by a T cell
(b) A closer look at antigen presentation
Antigen fragment
MHCmolecule
Host cell
Top view
AP Biology© 2011 Pearson Education, Inc.
Animation: Role of B Cells Right-click slide / select “Play”
AP Biology
Attack of the Killer T cells
Killer T cellbinds toinfected
cell
Destroys infected body cells binds to target cell secretes perforin protein
punctures cell membrane of infected cell apoptosis
infected celldestroyed
cell membrane
Killer T cell
cell membrane
target cell
vesicle
perforin puncturescell membrane
AP Biology
Immune system & Blood typeblood type
antigenon RBC
antibodiesin blood
donationstatus
A type A antigenson surface of RBC
anti-B antibodies __
B type B antigenson surface of RBC
anti-A antibodies __
ABboth type A & type B
antigens on surface of RBC
no antibodiesuniversal recipient
O no antigens on surface of RBC
anti-A & anti-B antibodies
universal donor
Matching compatible blood groups is critical for blood transfusions
A person produces antibodies against foreign blood antigens
© 2011 Pearson Education, Inc.
Animation: Helper T Cells Right-click slide / select “Play”
AP Biology© 2011 Pearson Education, Inc.
Animation: Cytotoxic T Cells Right-click slide / select “Play”
AP Biology
Figure 43.16
Antigen-presentingcell
Pathogen
Antigen fragment
Class II MHC moleculeAccessory proteinAntigen receptor
Helper T cell
Cytokines
Humoralimmunity
Cell-mediatedimmunity
B cellCytotoxic T cell
3
2
1
AP Biology
Figure 43.17-1
Cytotoxic T cell
1
Accessoryprotein
Class I MHCmolecule
Infectedcell
Antigenreceptor
Antigenfragment
AP Biology
Figure 43.17-2
Cytotoxic T cell
1 2
Accessoryprotein
Class I MHCmolecule
Infectedcell
Antigenreceptor
Antigenfragment
Perforin
Pore
Gran-zymes
AP Biology
Figure 43.17-3
Cytotoxic T cell
31 2
Accessoryprotein
Class I MHCmolecule
Infectedcell
Antigenreceptor
Antigenfragment
Perforin
Pore
Gran-zymes
ReleasedcytotoxicT cell
Dyinginfected cell
AP Biology
Immune system malfunctions Auto-immune diseases
immune system attacks own molecules & cells lupus
antibodies against many molecules released by normal breakdown of cells
rheumatoid arthritis antibodies causing damage to cartilage & bone
HIV Helper T cells attacked by virus
multiple sclerosis T cells attack myelin sheath of brain & spinal cord nerves
Allergies over-reaction to environmental antigens
allergens = proteins on pollen, dust mites, in animal saliva
stimulates release of histamine
AP Biology
Figure 43.22
IgE
Allergen
Histamine
Granule
Mast cell
AP Biology
Figure 43.23
AP Biology
Human Immunodeficiency Virus virus infects helper T cells
helper T cells don’t activate rest of immune system: killer T cells & B cells
also destroys helper T cells
AIDS: Acquired ImmunoDeficiency Syndrome infections by opportunistic
diseases death usually from “opportunistic” infections
pneumonia, cancers
HIV & AIDS
HIV infected T cell
AP Biology© 2011 Pearson Education, Inc.
Animation: HIV Reproductive Cycle Right-click slide / select “Play”
AP Biology
Latency AIDS
Helper T cellconcentration
Years after untreated infection
Hel
per
T c
ell c
on
cen
trat
ion
(in
blo
od
(ce
lls/m
m3 )
Relative anti-HIV antibodyconcentration
Relative HIVconcentration
800
600
400
200
00 1 2 3 4 5 6 7 8 9 10
Figure 43.25
AP Biology
Review Videos Bioflix: Immune response Bozeman Biology: Immune System video Why are you still alive? The Immune
System video by Kurz Gesagt The Lymphatic System video by Tammy
Moore
AP Biology
Concept check questions 43.1: 1, 2, 3 43.2: 2 43.3: 1, 3 43.4: 1, 2, 3
Test Your Understanding 2, 3, 4, 5, 6, 7